Establishment of novel marker and therapy by targeting PDCD4 for castration resistant prostate cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18600
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Fujita Health University
• Principal Investigator: Zennami Kenji 藤田医科大学, 医学部, 講師 (60440731)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Prostate cancer / translation / PDCD4 / eIF4a

Outline of Final Research Achievements

In the current study, we aimed to clarify the mechanism of castration resistant prostate cancer (CRPC), and to establish a novel therapy targeting miR-21/PDCD4 pathway.
Immunohistochemical evaluation using human prostate cancer specimens, Gleason score (GS) was inversely associate with PDCD4 expression. Androgen deprivation therapy elevated PDCD4 expression in high GS cases. Silvestrol, which is an inhibitor of translation associated protein, eIF4a showed antitumor effect in both LNCaP-sh-control and LNCaP-sh-PDCD4. Silvestrol showed significantly higher antitumor effect in sh-PDCD4 than that of sh-control. These results suggest that silvestrol might be a novel drug for CRPC in the future.

Free Research Field

Urologic oncology

Academic Significance and Societal Importance of the Research Achievements

本研究では前立腺組織あるいは前立腺癌組織内でのPDCD4発現レベルや分布を明らかにし、PDCD4経路をターゲットとした新規治療開発の重要性を見出した。
また、PDCD4は蛋白翻訳に重要な役割を持つeIF4aに対するinhibitorとしての機能が報告されているが、同様の機能を持つ薬剤(Silvestrol)は、PDCD4発現が低下した去勢抵抗性前立腺癌(CRPC)に対する抗腫瘍効果を認め、新規治療法となりうる可能性が示唆された。
これらの知見により、PDCD4経路は治療困難なCRPCの新規マーカー、治療となる可能性が示唆された。